Although Parkinson's disease has been considered the archetypal non-genetic disorder, recent analysis has shown that it is, in fact, at least partly genetic in origin with variability in 3 genes (synuclein, parkin and ubiqutin hydrolase)known to be associated with the disease and 7 genetic linkages identified but not resolved. Our work, in collaboration with the Bob Nussbaum (NHGRI) and with Katrina Gwinn-Hardy (Fischbeck lab: NINDS). We are working on collecting families with Parkinson's disease and carrying out genetic analysis of known genes and will be carrying out linkage analysis and positional cloning to try and identify new loci for this prevalent disorder. One surprising feature of our work has been that we have found that spinocerebellar ataxias can masquerade as Parkinson's disease in African and Asian populations. Last year, we have made an extremely important finding: that some cases of Parkinson's disease are caused by a chromosomal abnormality which causes a triplication ofthe synuclein gene. Others have confirmed this. This finding implicates the synuclein protein in the cell death process of all cases of Parkinson's disease. This year, we showed that a consequence of that finding was that individuals with the mitation had double their blood synuclein levels.